Dupilumab for Eosinophilic Gastrointestinal Diseases

(ENGAGE Trial)

Recruiting at 82 trial locations

Overseen By Clinical Trials Administrator

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Regeneron Pharmaceuticals

Disqualifiers: Weight < 40 kg, Helicobacter pylori, Crohn's, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

22 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called dupilumab to see if it can help people aged 12 and older who have a condition that causes too many white blood cells to gather in their stomach and small intestine, leading to inflammation and damage. The study will compare the effects of dupilumab to another treatment and will also look at side effects and how the body reacts to the drug.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that the use of any prohibited medications during the study is not allowed. It's best to discuss your current medications with the study team to see if they are allowed.

Is dupilumab generally safe for humans?

Dupilumab has shown a favorable safety profile with few, reversible side effects in clinical trials for conditions like atopic dermatitis, asthma, and nasal polyps. However, some patients have experienced ocular (eye-related) adverse reactions and eosinophilia (high levels of a type of white blood cell). ^{1 2 3 4 5}

How is the drug Dupilumab unique for treating eosinophilic gastrointestinal diseases?

Dupilumab is unique because it is a monoclonal antibody that targets the IL-4 and IL-13 signaling pathways, which are involved in allergic and inflammatory responses. Unlike other treatments, it has shown promise in achieving remission in patients with eosinophilic gastrointestinal disorders who did not respond to standard therapies. ^{4 5 6 7 8}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

Adults and adolescents aged 12+ with active eosinophilic gastritis (EoG), not just duodenitis, can join this trial. They must have a history of EoG symptoms, documented diagnosis, and meet specific symptom severity scores. Exclusions include Helicobacter pylori infection, certain dietary changes before screening, major upcoming surgery, other gastric conditions like Crohn's disease or past dupilumab use.

Inclusion Criteria

I've had at least 2 episodes of gastrointestinal symptoms weekly in the last 8 weeks.

I am a teenager and my country allows me to join this study.

I was diagnosed with Eosinophilic gastritis through a biopsy at least 3 months ago.

Exclusion Criteria

My body weight is under 40 kg.

I have previously participated in a dupilumab trial or have been treated with dupilumab.

I am currently on tube feeding or IV nutrition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A or B

Participants receive either dupilumab or placebo in a 24-week double-blind phase

24 weeks

Part C

28-week extension where all participants receive dupilumab

28 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dupilumab

Trial Overview The study tests the safety and effectiveness of an experimental drug called dupilumab in two different doses compared to a placebo for treating EoG with or without EoD. It will also examine how much drug is in the blood over time and if the body creates antibodies against it.

Participant Groups

Group I: Dupilumab Experimental Treatment 1 Intervention

Part A: Treatment Period Part C: Extended Treatment Period Eligible participants from Part A will enter Part C

Dupilumab is already approved in United States, European Union for the following indications:

Approved in United States as Dupixent for:

• Atopic dermatitis
• Asthma
• Chronic rhinosinusitis with nasal polyps
• Eosinophilic esophagitis

Approved in European Union as Dupixent for:

• Atopic dermatitis
• Asthma
• Chronic rhinosinusitis with nasal polyps
• Eosinophilic esophagitis

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

Dupilumab (Dupixent) has been associated with a risk of ocular adverse reactions, highlighting the importance of monitoring patients for eye-related side effects during treatment.

Prompt management of any ocular issues is essential for patients receiving dupilumab, ensuring their safety and well-being while benefiting from the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety update: dupilumab and ocular adverse reactions. [2022]

In a review of 22 studies involving 3303 patients, dupilumab demonstrated significant efficacy in treating atopic dermatitis, with 85.1% of patients achieving at least a 50% improvement in their Eczema Area and Severity Index (EASI) score after 16 weeks of treatment.

While dupilumab is generally well-tolerated, conjunctivitis was the most common side effect, occurring in 26.1% of patients, highlighting the need for ongoing monitoring of adverse events in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence of dupilumab efficacy and risk of adverse events: A systematic review and meta-analysis. Halling, AS., Loft, N., Silverberg, JI., et al.[2021]

Dupilumab is an effective treatment for type 2 inflammatory diseases like atopic dermatitis, asthma, and nasosinusal polyposis, as it inhibits the IL-4 receptor, blocking the action of key cytokines involved in these conditions.

The drug has a favorable safety profile, with few and reversible side effects, making it a promising option for patients who do not respond well to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dupilumab: beyond atopic dermatitis, off-label use in dermatology]. Russo, G., Laffitte, E.[2023]

Dupilumab, a monoclonal antibody used to treat conditions like asthma and atopic dermatitis, can cause hypereosinophilia (high eosinophil levels) as a potential adverse effect, which poses a challenge for clinicians.

An algorithm has been proposed to help manage dupilumab-induced hypereosinophilia, allowing for proper investigation of related health issues while minimizing unnecessary discontinuation of the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management. Caminati, M., Olivieri, B., Dama, A., et al.[2022]

Dupilumab is a monoclonal antibody that targets the IL-4 receptor, effectively inhibiting the action of IL-4 and IL-13, which are key players in allergic diseases.

It received its first approval in March 2017 for treating moderate-to-severe atopic dermatitis in adults who do not respond well to topical treatments, and is also being developed for asthma, nasal polyps, and eosinophilic esophagitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab: First Global Approval. Shirley, M.[2022]

In a real-life study of 12 patients with severe type-2 asthma, dupilumab treatment for 3 months led to significant improvements in asthma control (ACT score) and lung function (FEV1), indicating its efficacy in managing symptoms.

The treatment also resulted in a notable reduction in FeNO levels, a biomarker for type-2 inflammation, although blood eosinophil counts did not show significant change, suggesting that dupilumab effectively targets the IL4/IL13 pathway in asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early effectiveness of type-2 severe asthma treatment with dupilumab in a real-life setting; a FeNO-driven choice that leads to winning management. Carpagnano, GE., Scioscia, G., Buonamico, E., et al.[2022]

Dupilumab, a monoclonal antibody that inhibits interleukin-4 and interleukin-13 signaling, showed promising results in achieving clinical and histopathologic remission in three pediatric patients with non-eosinophilic esophagitis gastrointestinal disorders (EGID) who did not respond to standard treatments.

This study suggests that dupilumab may be a potential new treatment option for pediatric patients with eosinophilic gastrointestinal disorders, as it effectively reduced mucosal eosinophilia in multiple segments of the gastrointestinal tract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case Series on the Use of Dupilumab for Treatment of Refractory Eosinophilic Gastrointestinal Disorders. Patel, N., Goyal, A., Thaker, A., et al.[2023]

Dupilumab is an effective monoclonal antibody treatment for several conditions, including chronic rhinosinusitis with nasal polyposis and asthma, highlighting its broad therapeutic applications.

While generally well-tolerated, dupilumab can cause delayed hyperpigmented injection site reactions, in addition to more common temporary injection site and ocular surface reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed Hyperpigmented Injection Site Reactions Due to Chronic Dupilumab Use. Pacheco, CS., White, KM.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety update: dupilumab and ocular adverse reactions. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Real-world evidence of dupilumab efficacy and risk of adverse events: A systematic review and meta-analysis. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

[Dupilumab: beyond atopic dermatitis, off-label use in dermatology]. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Dupilumab: First Global Approval. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Early effectiveness of type-2 severe asthma treatment with dupilumab in a real-life setting; a FeNO-driven choice that leads to winning management. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A Case Series on the Use of Dupilumab for Treatment of Refractory Eosinophilic Gastrointestinal Disorders. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Delayed Hyperpigmented Injection Site Reactions Due to Chronic Dupilumab Use. [2023]